The present invention relates to a liquid chromatograph/mass spectrometer (LC/MS), and particularly to an automatic control of an LC/MS.
An analysis using an LC/MS is performed under certain measurement conditions, which, for example, include the condition of supplying the carrier liquid in the liquid chromatograph part (LC part); the condition for starting/ending the measurement in the mass spectrometer part (MS part); the range of mass numbers to be measured; the measurement mode (selected, for example, from MS mode, MS/MS mode and MSn mode). These measurement conditions are often changed from time to time in an analysis. For this type of analysis, the user prepares beforehand a xe2x80x9cmethodxe2x80x9d, which is a time schedule for changing the measurement conditions, while taking into consideration the content of the analysis. The method is stored beforehand in the controller. In a measurement, the controller controls every part of the LC/MS according to the method.
In an analysis using the LC/MS, when the component to be analyzed is known or specified, the time point at which the peak of the objective component appears in the chromatogram (i.e. retention time) can be calculated if the condition of supplying the carrier liquid in the LC part is determined, and also the time point at which the objective component enters the MS part can be calculated. In this case, unnecessary data collection can be avoided if the MS part collects the data only within a certain time period in which the peak passes the MS part. When, on the other hand, the component to be analyzed is unknown (e.g. when impurities are to be detected), it is impossible to know beforehand the time point at which the peak appears. In such a case, one possible measure is to collect all the measurement data over a broad range of mass numbers taking a long period of time and to store the data in a storage device (e.g. hard disk drive). This, however, wastes a large amount of storage space because the information thus collected contains a lot of unnecessary data corresponding to the non-peak sections of the chromatogram (FIG. 5).
A chromatograph/mass spectrometer constructed in view of the above problem is disclosed in the Japanese Examined Patent Publication No. H5-24458 (matured to Japanese Patent No. 1816212). In this chromatograph/mass spectrometer, data of the total ion chromatogram (TIC) collected by a measurement are temporarily stored in an auxiliary memory such as a semiconductor memory. The time range corresponding to the peak or peaks of the chromatogram is identified by analyzing the above data, and only those measurement data within the identified time range are stored in the storage device. For this construction, however, an auxiliary memory operating at a high-speed and having a large capacity is necessary to temporarily store a large amount of data of the total ion chromatogram. Particularly, when the MS part is a time-of-flight (TOF) type, the size of data collected in a mass-scanning operation reaches several hundreds of kilobytes to several megabytes. Furthermore, it is necessary to repeat the mass-scanning from several to more than ten times to adequately analyze the waveform of a chromatogram. To store such a large amount of data, it is necessary to use an expensive semiconductor memory with a large capacity, which increases the production cost.
When the MS part is an ion trap type, the following problem must be considered. In the ion trap mass spectrometer, the trapping space within the electrodes has a limited capacity of ions at a time because of the space charges due to the trapped ions. Therefore, the range (or dynamic range) in which the concentration of the component can be linearly measured is limited to a certain extent. In a conventional improvement, the time period of introducing ions into the ion trap is appropriately restricted according to the concentration of the sample coming from the LC part to increase the apparent dynamic range (i.e. to raise the upper limit). An example of the known methods of automatically carrying out the above operation is Automatic Sensitivity Control (ASC). By this method, the change in the sample concentration is monitored based on the data collected in the previous mass-scanning operation. When the sample concentration is high, the time period of introducing ions into the ion trap is temporarily shortened, as shown in FIG. 6, to prevent the trapping space from being overfilled with the space charges. By this method, however, when a sudden rise of the peak occurs in the chromatogram, the feedback process cannot keep up with the rise in time, which causes a delay of control and yields a distorted chromatogram, as shown in FIG. 7.
When the A/D converter at the output of the ion detector of the MS part has a poor resolving power (or small quantifying bit number), the dynamic range is accordingly narrow. In such a case, it is possible to increase the apparent dynamic range by appropriately switching the gain of the analog amplifier according to the strength of the signal of the ion detector, i.e. by lowering the gain when the strength of the signal is great. In the TOF type of MS, however, it is necessary to A/D-convert the signal at a speed as high as about 500 MHz to several GHz. At such a high speed, the switching speed of the gain of the analog amplifier is slower than the A/D conversion speed, so that a delay of control appears as shown in FIG. 7 in a real-time measurement.
The present invention proposes an LC/MS constructed so that only necessary data are collected efficiently and that the apparent dynamic range of the MS part can be appropriately changed according to the concentrations of the sample components coming from the LC part.
A liquid chromatograph/mass spectrometer according to the present invention includes:
a mass spectrometer provided as a main detector;
an auxiliary detector provided apart from the mass spectrometer;
a passage for introducing a sample from the liquid chromatograph part first to the auxiliary detector and then to the mass spectrometer part with a delay of a preset time period;
a peak detector for analyzing a chromatogram constructed from an output signal of the auxiliary detector to determine a retention time of each peak in the chromatogram; and
a controller for controlling a measurement operation of the mass spectrometer according to the retention time of the peak or peaks in the chromatogram.
The features of the present invention will be clearly understood from the detailed description of a preferred embodiment with reference to the attached drawings.